The oxygenation of polyunsaturated fatty acids to prostaglandins is catalyzed by the membrane bound enzyme complex prostaglandin synthetase, whih is widely distributed in mammalian tissue. We have recently found that during the early stages of oxygenation a variety of xenobiotics, including the carcinogenic hydrocarbon benzopyrene, are co-oxygenated. Hydroperoxide intermediates of prostaglandin biosynthesis appear to be responsible for this co-oxygenation by interacting with an unidentified microsomal enzyme. We propose to study this co-oxygenase activity, the nature of the actual oxidizing species generated, and the identity of the enzyme which interacts with the hydroperoxide to produce it. Since an important first step in the "metabolic activation" of polycyclic aromatic hydrocarbons is oxygenation to a derivative which is capable of binding to DNA, it is conceivable that the hydroperoxide dependent oxygenations which we propose to study are important in the initiation of tumor formation in mammals. In addition, the biosynthesis of prostaglandins has been suggested to be involved in inflammation. The major role which a number of non-steroidal drugs play in relieving the symptoms of inflammation has been proposed to be due to their ability to inhibit prostaglandin synthetase. Since these anti-inflammatory agents inhibit co-oxygenation triggered by the synthetase as well, it is conceivable that the non-specific oxidation of normal tissue constituents could play a role in the inflammatory response. Finally, the long term effects of prostaglandin synthetase stimulated co-oxygenation in somatic cells could lead the development of various pathological states and eventually to cell death. The present experiments have been designed to provide a basis on which to evaluate these possibilities.